Pharmacokinetics of the combination raltegravir/atazanavir in HIV-1-infected patients

Abstract

Objectives: To evaluate the use of raltegravir with unboosted atazanavir in combination with one nucleoside reverse transcriptase inhibitor (NRTI) (lamivudine or emtricitabine) as a potentially well-tolerated once-daily (qd) maintenance regimen.

Methods: We compared the pharmacokinetics of raltegravir 400 mg twice daily (bid) with raltegravir 800 mg qd in HIV-infected patients (n=17) on unboosted atazanavir (600 mg qd) in combination with lamivudine or emtricitabine.

Results: The area under the plasma concentration vs. time curve for a dose interval t (AUC0 -t ) of 800 mg qd divided by 2 was not significantly different from the AUC0 -t of 400 mg bid (P=0.664) but the minimum concentration (C min ) was 72% lower with the qd regimen (P=0.002). The regimen was well tolerated and the viral load remained undetectable in all patients during the 6 weeks of the study follow-up.

Conclusions: A qd regimen of raltegravir 800 mg, atazanavir 600 mg and lamivudine or emtricitabine resulted in favourable pharmacokinetic profiles and good short-term safety and efficacy data. Larger phase IIb studies are needed to explore this novel regimen.

Trial registration: ClinicalTrials.gov NCT00943540.

Keywords: HIV integrase inhibitor; antiretroviral agents; atazanavir; drug interactions; pharmacokinetics; raltegravir.